ENTRY       hsa01522                    Pathway
NAME        Endocrine resistance - Homo sapiens (human)
DESCRIPTION Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SERMs, e.g. tamoxifen), estrogen synthesis inhibitors (e.g. aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane), and selective estrogen receptor down-regulators (SERDs, e.g. fulvestrant). However, resistance to these agents has become a major clinical obstacle. Mechanisms of endocrine resistance include loss of ER-alpha expression, altered expression of coactivators or coregulators that play a critical role in ER-mediated gene transcription, ligand-independent growth factor signaling cascades that activate kinases and ER-phosphorylation, altered availability of active tamoxifen metabolites regulated by drug-metabolizing enzymes, such as CYP2D6, and deregulation of the cell cycle and apoptotic machinery.
CLASS       Human Diseases; Drug resistance: antineoplastic
PATHWAY_MAP hsa01522  Endocrine resistance
DRUG        D03793  Ilomastat (USAN/INN)
            D03795  Marimastat (USAN/INN)
            D03797  Prinomastat (USAN/INN)
            D03802  Tanomastat (USAN/INN)
            D07928  Ethinylestradiol propanesulfonate
            D11262  Andecaliximab (USAN/INN)
ORGANISM    Homo sapiens (human) [GN:hsa]
REFERENCE   PMID:23344024
  AUTHORS   Garcia-Becerra R, Santos N, Diaz L, Camacho J
  TITLE     Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance.
  JOURNAL   Int J Mol Sci 14:108-45 (2012)
            DOI:10.3390/ijms14010108
REFERENCE   PMID:19701242
  AUTHORS   Musgrove EA, Sutherland RL
  TITLE     Biological determinants of endocrine resistance in breast cancer.
  JOURNAL   Nat Rev Cancer 9:631-43 (2009)
            DOI:10.1038/nrc2713
REFERENCE   PMID:22015292
  AUTHORS   Giuliano M, Schifp R, Osborne CK, Trivedi MV
  TITLE     Biological mechanisms and clinical implications of endocrine resistance in breast cancer.
  JOURNAL   Breast 20 Suppl 3:S42-9 (2011)
            DOI:10.1016/S0960-9776(11)70293-4
REFERENCE   PMID:25907219
  AUTHORS   Ma CX, Reinert T, Chmielewska I, Ellis MJ
  TITLE     Mechanisms of aromatase inhibitor resistance.
  JOURNAL   Nat Rev Cancer 15:261-75 (2015)
            DOI:10.1038/nrc3920
REFERENCE   PMID:24841429
  AUTHORS   Viedma-Rodriguez R, Baiza-Gutman L, Salamanca-Gomez F, Diaz-Zaragoza M, Martinez-Hernandez G, Ruiz Esparza-Garrido R, Velazquez-Flores MA, Arenas-Aranda D
  TITLE     Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review).
  JOURNAL   Oncol Rep 32:3-15 (2014)
            DOI:10.3892/or.2014.3190
REFERENCE   PMID:26849149
  AUTHORS   Luqmani YA, Alam-Eldin N
  TITLE     Overcoming Resistance to Endocrine Therapy in Breast Cancer: New Approaches to a Nagging Problem.
  JOURNAL   Med Princ Pract 25 Suppl 2:28-40 (2016)
            DOI:10.1159/000444451
REFERENCE   PMID:22771991
  AUTHORS   Bianco S, Gevry N
  TITLE     Endocrine resistance in breast cancer: from cellular signaling pathways to epigenetic mechanisms.
  JOURNAL   Transcription 3:165-70 (2012)
            DOI:10.4161/trns.20496
REFERENCE   PMID:20887199
  AUTHORS   Osborne CK, Schiff R
  TITLE     Mechanisms of endocrine resistance in breast cancer.
  JOURNAL   Annu Rev Med 62:233-47 (2011)
            DOI:10.1146/annurev-med-070909-182917
REFERENCE   PMID:23714450
  AUTHORS   Miller TW
  TITLE     Endocrine resistance: what do we know?
  JOURNAL   Am Soc Clin Oncol Educ Book 0011300037 (2013)
            DOI:10.1200/EdBook_AM.2013.33.e37
REFERENCE   PMID:23625614
  AUTHORS   Lonning PE, Eikesdal HP
  TITLE     Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.
  JOURNAL   Endocr Relat Cancer 20:R183-201 (2013)
            DOI:10.1530/ERC-13-0099
REFERENCE   PMID:26473850
  AUTHORS   Egeland NG, Lunde S, Jonsdottir K, Lende TH, Cronin-Fenton D, Gilje B, Janssen EA, Soiland H
  TITLE     The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.
  JOURNAL   Int J Mol Sci 16:24243-75 (2015)
            DOI:10.3390/ijms161024243
REFERENCE   PMID:24130921
  AUTHORS   Chang M
  TITLE     Tamoxifen resistance in breast cancer.
  JOURNAL   Biomol Ther (Seoul) 20:256-67 (2012)
            DOI:10.4062/biomolther.2012.20.3.256
REFERENCE   PMID:18804516
  AUTHORS   Zilli M, Grassadonia A, Tinari N, Di Giacobbe A, Gildetti S, Giampietro J, Natoli C, Iacobelli S
  TITLE     Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer.
  JOURNAL   Biochim Biophys Acta 1795:62-81 (2009)
            DOI:10.1016/j.bbcan.2008.08.003
REFERENCE   PMID:24289103
  AUTHORS   Mo Z, Liu M, Yang F, Luo H, Li Z, Tu G, Yang G
  TITLE     GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer.
  JOURNAL   Breast Cancer Res 15:R114 (2013)
            DOI:10.1186/bcr3581
REFERENCE   PMID:24415977
  AUTHORS   Hasson SP, Rubinek T, Ryvo L, Wolf I
  TITLE     Endocrine resistance in breast cancer: focus on the phosphatidylinositol 3-kinase/akt/mammalian target of rapamycin signaling pathway.
  JOURNAL   Breast Care (Basel) 8:248-55 (2013)
            DOI:10.1159/000354757
REFERENCE   PMID:15613444
  AUTHORS   Ring A, Dowsett M
  TITLE     Mechanisms of tamoxifen resistance.
  JOURNAL   Endocr Relat Cancer 11:643-58 (2004)
            DOI:10.1677/erc.1.00776
REFERENCE   PMID:24565562
  AUTHORS   Ribeiro JR, Freiman RN
  TITLE     Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer.
  JOURNAL   J Steroid Biochem Mol Biol 143:160-73 (2014)
            DOI:10.1016/j.jsbmb.2014.02.010
REFERENCE   PMID:20960099
  AUTHORS   Wang D, Hu L, Zhang G, Zhang L, Chen C
  TITLE     G protein-coupled receptor 30 in tumor development.
  JOURNAL   Endocrine 38:29-37 (2010)
            DOI:10.1007/s12020-010-9363-z
REFERENCE   PMID:26122181
  AUTHORS   Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R
  TITLE     ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer.
  JOURNAL   Nat Rev Clin Oncol 12:573-83 (2015)
            DOI:10.1038/nrclinonc.2015.117
REL_PATHWAY hsa00982  Drug metabolism - cytochrome P450
            hsa04010  MAPK signaling pathway
            hsa04024  cAMP signaling pathway
            hsa04110  Cell cycle
            hsa04151  PI3K-Akt signaling pathway
            hsa04210  Apoptosis
            hsa04330  Notch signaling pathway
            hsa04913  Ovarian steroidogenesis
KO_PATHWAY  ko01522
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